This document provides information on Inflammatory Bowel Disease (IBD), which includes Crohn's Disease and Ulcerative Colitis. It discusses the types of IBD, symptoms, investigations, complications, and treatments. The two main types are Crohn's Disease, which causes transmural inflammation of the GI tract, and Ulcerative Colitis, which causes mucosal inflammation confined to the colon and rectum. Symptoms and complications are described for each condition. Investigations include blood tests, endoscopy, and imaging. Treatments aim to induce and maintain remission, and include medications like aminosalicylates, corticosteroids, immunosuppressants, biologics, and antibiotics

1. Presented by,
THUSHARA. C
1ST YEAR MPHARM
PHARMACY PRACTICE

2. Inflammatory Bowel
Disease
Inflammatory bowel disease (IBD) is a
group of long-term conditions that cause
inflammation of the gastrointestinal tract
(gut)

3. There are two forms of idiopathic
inflammatory bowel disease (IBD):
CROHN’S DISEASE: A transmural
inflammation of GI mucosa that may
occur in any part of the GI tract
ULCERATIVE COLITIS: A mucosal
inflammatory condition confined to the
rectum and colon.

4. TYPES
Crohn’s disease
 Extends into the deeper
layers of the intestinal wall,
and may affect the mouth,
esophagus, stomach, and
small intestine.
 Transmural inflammation
and skip lesions.
 In 50% cases -
ileocolic,30% ileal and 20%
-colic region.
 Regional enteritis
Ulcerative colitis
 causes ulceration and
inflammation of the inner
lining of the colon and
rectum.
 It is usually in the form of
characteristic ulcers or
open sores.

6. ETIOLOGY
Immunology
Initiating pathogen
Environmental Factors
Genetic factors

7.  Bacterial antigens are taken up by specialized M cells,
pass between leaky epithelial cells or enter the lamina
propria through ulcerated mucosa
 After processing they are presented on type 1 T-helper
cells by antigen presenting cells (APC) in the lamina
propria.
 T-cell activation and differentiation results in Th1 T cell
mediated cytokine response
 With the secretion of cytokines including gamma
interferon (IFNƴ)
PATHOPHYSIOLOGY

8. Further amplification of T cells perpetuates the inflammatory
process with activation of non immune cells and release of the
important cytokines.
Eg: IL-12, IL-23, IL-1, IL-6 and tumor necrosis factor (TNF)
These pathways occur in all normal individual exposed to
inflammatory insults and this is self limiting in healthy subjects
In genetically predisposed persons, dysregulation of innate
immunity may trigger inflammatory bowel disease.

9. Smoking appears to be protective for
ulcerative colitis but associated with
increased frequency of Crohn’s disease.
Ulcerative colitis and Crohn’s disease
differ in two general respects: anatomic
sites and depth of involvement within the
bowel wall. There is, however, overlap
between the two conditions, with a small
fraction of patients showing features of
both diseases

10. ULCERATIVE COLITIS
 Ulcerative colitis is confined to the colon
and rectum and affects primarily the
mucosa and the submucosa.
 The primary lesion occurs in the crypts of
the mucosa in the form of a crypt abscess.
 Local complications (involving the colon)
occur in the majority of ulcerative colitis
patients. Relatively minor complications
include hemorrhoids, anal fissures, or
perirectal abscesses.

11.  The patient with toxic megacolon usually
has a high fever, tachycardia, distended
abdomen, elevated white blood cell count,
and a dilated colon.
 ulcerative colitis have hepatobiliary
complications including fatty liver,
pericholangitis, chronic active hepatitis,
cirrhosis, sclerosing cholangitis,
cholangiocarcinoma, and gallstones.

12.  Arthritis commonly occurs in IBD patients
and is typically asymptomatic and
migratory. Arthritis typically involves one or
a few large joints such as the knees, hips,
ankles, wrists, and elbows

13. CROHN’S DISEASE
 Crohn’s disease is a transmural
inflammatory process. The terminal
ileum is the most common site of the
disorder but it may occur in any part of
the GI tract.
 Patients often have normal bowel
separating segments of diseased bowel;
that is, the disease is often
discontinuous.

14.  Complications of Crohn’s disease may
involve the intestinal tract or organs
unrelated to it. Small-bowel stricture and
subsequent obstruction is a complication
that may require surgery. Fistula
formation is common and occurs much
more frequently than with ulcerative
colitis.

15.  Systemic complications of Crohn’s
disease are common and similar to
those found with ulcerative colitis.
Arthritis, iritis, skin lesions, and liver
disease often accompany Crohn’s
disease.
 Nutritional deficiencies are common
with Crohn’s disease.

17. Ulcerative Colitis

18. Crohn’s Disease –
Macroscopic Features

19. Crohn’s disease – sign and
symptoms
 Colitis and perianal disease
- low grade fever, malaise, diarrhea, crampy abdominal
pain, sometimes hematochezia
- pain is caused by passage of fecal material through
narrowed and inflamed segments of large bowel
 Gastroduodenal disease
- nusea, vomiting, epigastric pain
- second portion of duodenum is more commonly
involved than the bulb

20.  INTESTINAL OBSTRUCTION IN CD:
 Postprandial bloating,cramping pains & loud
borborygmi
 (narrowing can occur due to inflammation
spasm
or fibrosis)
FISTULATING DISEASE:
Can result in intra abdominal or retroperitoneal
abscess menifested by fever chills, a tender
abdominal mass & leucocytosis.

21.  Enterocolic fistulas :
presents with diarrhoea , weight loss &
malnutrition.
 Enterovesical fistulas/enterovaginal
fistulas:
presents with recurrent infections.
 Enterocutaneous fistulas:
usually develop at site of surgical scars.

22. Endoscopic image of Crohn's colitis showing deep ulceration.

24. EXTRA INTESTINAL MANIFESTATIONS

25. Ulcerative colitis – clinical
presentation
 The major symptoms of UC are:
 Bloody diarrohea(hallmark)
 Tenesmus
 Passage of mucus
 Crampy abdominal pain

26.  Patients with proctitis usually pass fresh blood or
blood-stained mucus either mixed with stool or
streaked onto the surface of normal or hard stool
 When the disease extends beyond the rectum, blood is
usually mixed with stool or grossly bloody diarrhea may
be noted
 When the disease is severe, patients pass a liquid
stool containing blood, pus, fecal matter
 Other symptoms in moderate to severe disease
include: anorexia, nausea, vomitting, fever, weight loss

27. MILD DISEASE (UC)
Gradual onset Infrequent diarrhoea
(<5movements/day)
Intermittent rectal bleeding. Stool may be
formed or too loose in consistency
Fecal urgency ,tenesmus,left lower
quadrant pain relieved by defecation
NO significant abdominal tenderness

28. MODERATE DISEASE
(UC)
 More severe diarrhoea with frequent
bleeding
 Abdominal pain & tenderness but not
severe
 Mild fever , anemia & hypoalbuminemia

29. SEVERE DISEASE (UC)
 Severe diarrhoea with >6-10 bloody bowel
movements /day
 Severe anemia , hypovolemia ,imparied nutrition
& hypoalbuminemia
 Abdominal pain & tenderness
 FULMINANT COLITIS:
 Subset of severe disease with rapidly
worsening symptoms & signs of toxicity

30. ulcerative colitis:the left side of the colon is affected
The image shows confluent superficial ulceration
and loss of mucosal architecture.

31. EXAMINATION
 PHYSICAL:
 Hydration & volume status determined by
B.P
 Pulse rate
 Nutritional status
 ABDOMINAL:
 Tenderness & evidence of peritoneal
inflammation
 Presence of red blood on DRE

32. INVESTIGATIONS
CD UC
Blood Test
•CP with morphology: Normocytic
normocromic anemia of chronic
disease
•Serum B12 level may be low.
•Raised ESR, CRP and raised WBC
count.
•Hypo albuminaemia.
•Blood culture in septicaemia.
•Fe deficiency anemia
•Raised white cell and platelet count
•Raised ESR, CRP
•Hypo albuminaemia
Serological Test
•Saccharamyces cerevisiae antibody
is usually present
•P-ANCA negative
•P-ANCA may be positive
Stool culture
•Should always be performed in both to rule out infective cause

33. CD UC
Radiology
Plain ABD. X-ray:
•Intestinal obstruction or displacement
of bowel loops by a mass.
•Extent of the disease can be judge by
air distribution in the colon and the
presence of colonic dialatation
Ultrasound:
•Thickened small bowel loops and
mesentery or abscess
•Thickening of colonic wall and
presence of free fluid in abdominal
cavity
Barium follow through:
•Asymmetrical alteration mucosal
pattern with narrowing or stricturing.
•Skip lesions
•Fine mucosal granularity
•Mucosa become thickenned and
superficial ulcers are seen (collar-
button ulcers)
•Loss of haustration

34. CD UC
Instant Barium enema
•Patchy sup. Ulceration to wide spread
deep (rose thorn ulcer)
•Cobble stone appearance and
narrowing
•Superficial ulcers
•Shortened and narrowed colon in
long standing disease
Colonoscopy
•Fissures and fistulae •Pseudopolyps
•Mucosal granularity and hyperemia
High resolution USG. And spiral CT
•Radionuclide scan with gallium
labeled polymorphs or indium or
technetium labeled leucocytes
•Capsule imaging of the gut.
•Radionuclide scan used to assess
colonic inflammation

37. TREATMENT
OBJECTIVES
IBD:
 Induce remission with control of acute
inflammatory flare.
 Maintain remission as long as possible.
 Normalize bowel function when
possible.
 Maintain nutritional status.
 Improve quality of life (QOL).

38. NON PHARMACOLOGICAL
TREATMENT
Nutritional Support
• Patients with moderate to severe IBD are often
malnourished.
• The nutritional needs of the majority of patients
can be adequately addressed with enteral
supplementation. Patients who have severe disease
may require a course of parenteral nutrition.
• Probiotic formulas have been effective in
maintaining remission in ulcerative colitis.

39. Surgery
 For ulcerative colitis, colectomy may be performed
when the patient has disease uncontrolled by
maximum medical therapy or when there are
complications of the disease such as colonic
perforation toxic dilatation (megacolon), uncontrolled
colonic hemorrhage, or colonic strictures.
 The indications for surgery with Crohn’s disease are
not as well established as they are for ulcerative
colitis, and surgery is usually reserved for the
complications of the disease. There is a high
recurrence rate of Crohn’s disease after surgery.

40. PHARMACOLOGICAL
TREATMENT
1.AMINOSALICYLATES:
Sulfasalazine, mesalazine, olsalazine, balsalazide
Effective therapy of UC, but little to no benefit for
CD.
MOA: varied mechanisms including blockade of
the infl ammatory mediators interleukin-1 and
tumor necrosis factor-alpha as well as modulation
of peroxisome proliferator activated receptor
colonic infl ammation is reduced.

41. Precautions and adverse effects:
Fever, dizziness, headache, itching,
rash,granulocytopenia, luecopenia,
thrombocytopenia, aplastic anemia,
hepatotoxicity, chronic renal injury
2. STEROIDS
 Glucocorticoid properties of hydrocortisone and
prednisolone are the mainstay of treatment in
active ulcerative colitis and Crohn's disease

42.  Prednisolone administered orally or rectally is the
steroid of choice although in emergency situations
hydrocortisone or methylprednisolone is used
when the parenteral route is required.
 Corticosteroids have direct anti-inflammatory and
immunosuppressive actions whichrapidly control
symptoms.
 They can be used either alone or in combination,
with a suitable mesalazine (5-aminosalicylic acid,
5-ASA) formulation or immunosuppressant, to
induce remission.

43.  Oral corticosteroids should not be used for
maintenance treatment because of serious
long-term side effects, and abrupt
withdrawal should be avoided.
 Formulations. Oral prednisolone will control
mild and moderate
 IBD and 70% of patients improve after 2–4
weeks of 40 mg/day. This is gradually
reduced over the next 4–6 weeks

44.  Mechanism of action. The glucocorticoid and
mineralocorticoid eff ects of the steroids used in
IBD are wide ranging. The anti-infl ammatory eff
ects are likely due to glucocorticoid suppression of
proinfl ammatory cytokines.
3. AZATHIOPRINE & 6-MERCAPTOPURINE
They are ef fective at inducing and maintaining
remission in IBD. Response is slow and may take
months to be fully effective.

45.  Mechanism of action. Azathioprine and 6-MP
are purine antimetabolite drugs, which
interferewith DNA synthesis, with disruption of the
infl ammatory response seen in IBD
 Precautions and adverse eff ects. Bone marrow
suppression. Both azathioprine and 6-MPhave
been implicated in increased risk for Epstein Barr
related non-Hodgkin lymphoma. This risk appears
to be small but is serious..

46. 4. METHOTREXATE: An effective treatment for
inducing remission, maintaining remission, and
steroid sparing in CD. Parenteral methotrexate is
also effectivefor maintaining remission in CD.
 Mechanism of action: Methotrexate is a folate
analog and inhibits dihydrofolate reductase with
multiple modes of anti-infl ammatory eff ects.
ADR: The most common risks are rash, nausea,
pneumonitis or Mycoplasma pneumonia, and
elevated serum transaminases. CD patients
treated with methotrexate appear to be at low risk
for hepatic toxicity

47. 5. Cyclosporine and tacrolimus
Immunosuppressive agents that have been
shown to be effective in IBD. They are typically
used for severe acute IBD
 Mechanism of action: Both cyclosporine and
tacrolimus are calcineurin inhibitors and are
potent inhibitors of T-lymphocyte activation

48.  Precautions and adverse events:
paresthesias, hypertension, hypertrichosis,
renal insuffi ciency, infection, gingival
hyperplasia and seizure.
Patients should be closely monitored for
effects on blood pressure, electrolytes, renal
function, and cholesterol. Hypocholesterolemia
and hypomagnesemia increase the risk of
seizure.

49. 6. BIOLOGICS
Infliximab , adalimumab , and certolizumab pegol
 These agents are anti-tumor necrosis factor-alpha
antibodies
 Anti-TNF-alpha therapy mechanism of action:
Tumor necrosis factor-alpha is a cytokine
involved in multiple proinflammatory and proliferative
pathways in IBD. These agents
bind TNF-alpha preventing its binding to cell surface
receptors and subsequently decreases inflammatory
cytokines and increasing apoptosis of activated T
lymphocytes and monocytes.

50. Adverse effects:
 All anti-TNF-alpha antibodies carry black box warnings
for increased risk of opportunistic infections (e.g.,
tuberculosis, invasive fungal infections such as
histoplasmosis, blastomycosis, or pneumocystis, viral
infections such as hepatitis B.
 Use of concomitant immunosuppressive agents may
increase risk of infection

51. 7.Antibiotics:
 Use of select antibiotics such as metronidazole,
ciprofloxacin, clofazimine, or rifaximin with the specifi c
goal of remission of acute IBD iscontroversial.
 Metronidazole and ciprofl oxacin are used widely by
convention as maintenance therapy in CD but
controlled trial results do not conclusively support this
use.
 Metronidazole has been useful in patients suffering
from pouchitis postbowel resection surgerythat involves
formation of a pouch.

52. 8. Antispasmodics and antidiarrheals:
 Cramping and abdominal IBS-like
symptoms are often noted in IBD patients
9.Analgesics:
There is rarely a need for pain control in UC as the
disease is limited to the mucosa of the colon with
limited involvement of tissue containing pain
receptors. Narcotics are to be avoided in UC
therapy outside of perioperative situations as they
increase the risk of toxic megacolon and can mask
signs of perforation. NSAID medications should be
avoided as they have been implicated in inducing
IBD flares.

53. ALGORITHM FOR UC
Ulcerative colitis
Inducing remission
Active/left sided
or extensive disease
Oral aminosalicylate plus oral
corticosteroids.If prompt
response is required plus rectal
aminosalicylate or corticosteroid
if rectal symptoms
Active distal disease
Topical aminosalicylate (suppositories
and enemas)or topical steroid plus oral
aminosalicylate or corticosteroid to give
prompt relief

54. Severe
Intravenous and rectal steroids,
fluids and electrolytes, heparin,
nutrition, antibiotics then
ciclosporin (or infliximab)
Maintenance
In order of preferred choice:
aminosalicylates, azathioprine,
mercaptopurine, infliximab
Nutrition: calcium and vitamin D
supplements

55. ALGORITHM FOR CD
Crohn’s disease
Inducing remission
Active ileal/ileocolonic disease
Corticosteroids; elemental or polymeric diet; parenteral
nutrition if complex fistulae; azathioprine or mercaptopurine as
adjunctive therapy Infliximab or adalimumab if response or
intolerance or contraindication to eithercorticosteroid and/or
Immunosuppressants Surgery if medical treatment fails
Fistulating and perianal disease
Antibiotics,Azathioprine or mercaptopurine
or methotrexate then infliximab and/or surgery;
Elemental or parenteral nutrition

56. Maintenance
Stop smoking; calcium and vitamin
D supplements
Azathioprine OR mercaptopurine OR
methotrexate and/or
infliximab/adalimumab
Post surgery
High dose mesalazine (ileal
resection only), azathioprine,
mercaptopurine, methotrexate
Chronic active and steroid
dependant
Azathioprine, mercaptopurine,
methotrexate or infliximab/adalimumab Adjunctive treatments including
analgesia, antidiarrhoeals, nutritional supplements (e.g. iron, vitamin B12,
calcium and vitamin D) may be necessary